This is the twice-per-month electronic newsletter for basic, preclinical and translational research news related to the Johns Hopkins School of Medicine. Please forward freely. Direct comments or questions to Joanna Downer, PhD, in the Office of Corporate Communications (410-614-5105, jdowner1@jhmi.edu).
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IN THIS ISSUE:
+ Diabetes-Related Erectile Dysfunction Clarified
+ Protein Linked to Growth of Organs and Cancer
+ IRF5 Targeted by Two Cancer Drugs In Vitro
NEWS BRIEFS:
Leroy Hood To Give Sept. 29 Lecture
100+ Women Professors Gala Nov. 1
IN THE NEWS:
Solomon Snyder in New Scientist
Doug Kerr on the CBS Early Show
Hal Dietz on NationalGeographic.com and in Science
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Do you have an interesting research finding about one month from publication or presentation? Send manuscripts to Joanna Downer at jdowner1@jhmi.edu or fax to 410-614-8951. Information about awards and honors received by laboratory personnel and others is welcomed also.
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RESEARCH HIGHLIGHTS:
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8/5/05
Diabetes-Related Erectile Dysfunction Clarified
By studying rats with diabetes, researchers at the Brady Urological Institute at Johns Hopkins have discovered that an over-supply of a simple blood sugar could be a major cause of erectile dysfunction in diabetic men.
Researchers have found that O-GlcNAc, a blood sugar present in hyperglycemic circumstances, interferes with the chain of events needed to achieve and maintain erection and can lead to permanent penile impairment over time. The results, which have implications for new types of erectile dysfunction treatments targeting this mechanism of erection, are described in the Aug. 16 issue of the Proceedings of the National Academy of Sciences.
Previous research had shown that diabetic erectile dysfunction was partially due to an interruption in enzyme that starts the chain of vascular events leading to an erection. O-GlcNAc causes that interruption, the researchers discovered.
"We were interested to determine whether high glucose in diabetes mellitus modifies the endothelial nitric oxide synthase (eNOS) enzyme, which is responsible for the achievement and maintenance of erection," says Biljana Musicki, PhD, lead investigator of the study and a research associate in the Brady Urological Institute.
Erectile dysfunction is a common problem for more than half of men with diabetes. However, this is not the same type of erectile dysfunction seen in non-diabetics, and it is less effectively treated with conventional drugs like Viagra.
The O-GlcNAc modification of proteins was initially discovered in the laboratory of Gerald Hart, PhD, professor and director of biological chemistry at Johns Hopkins.
http://www.hopkinsmedicine.org/Press_releases/2005/08_09_05.html
PNAS 16 Aug. 2005;102(33):11870-11875.
http://www.pnas.org/cgi/content/full/102/33/11870
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8/12/05
Protein Linked to Growth of Organs and Cancer
Johns Hopkins scientists have identified a protein in fruit flies whose counterpart in humans may help cause cancer.
The researchers report in the Aug. 12 issue of Cell that a protein dubbed Yorkie directly controls the fruit fly's organ size and, when overabundant, causes increased cell growth and decreased cell death, hallmarks of cancer. Yorkie's mammalian relative, called YAP, appears to do the same thing, the researchers report, which suggests that in humans, a defect in the gene that makes YAP might contribute to cancer.
"We were surprised to find that by adding Yorkie to levels greater than normal, the fruit fly's organs grew larger," says Duojia Pan, PhD, who carried out most of the study at the University of Texas Southwestern Medical Center at Dallas before coming to the Johns Hopkins Institute for Basic Biomedical Sciences. "Likewise, levels of Yorkie below normal caused the fruit fly's organs to be smaller than usual."
The new findings build on Pan's earlier studies, which showed that fruit flies missing a gene called hippo developed tumors. That study revealed a tumor-suppression pathway involving proteins made by hippo and two other like-minded genes, all three of which function in a chain reaction to chemically add phosphate to other proteins, a process called phosphorylation. The new study shows that Yorkie is a critical target of hippo.
http://www.hopkinsmedicine.org/Press_releases/2005/08_11_05.html
Cell 12 Aug. 2005;122(3):421-434.
http://dx.doi.org/10.1016/j.cell.2005.06.007
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8/15/05
IRF5 Targeted by Two Standard Cancer Drugs In Vitro
In studies with cell lines, Johns Hopkins Kimmel Cancer Center scientists have found that interferon, used for 30 years to treat blood cancers, multiple sclerosis and hepatitis, selectively kills colon cancer cells when combined with another standard chemotherapy agent, irinotecan (CPT-11). The study is published in the Aug. 15 issue of Cancer Research.
The new findings suggest that the combination tactic, which targets a common gene pathway in colon cancer cells, could be more potent than either drug alone, and has fewer side effects.
Specifically, the team's studies reveal that both drugs increase levels of IRF5 (interferon regulatory factor-5), which works as a tumor suppressor to halt cancer cell growth. The researchers had discovered that IRF5 is turned off completely by many cancers, but most colon cancers retain low levels of the suppressor protein.
"We believe that interferon and irinotecan both work to increase IRF5 protein levels in these cells, but irinotecan activates the protein in the final step to initiate cancer cell death," says Betsy Barnes, PhD, assistant professor of oncology and lead researcher.
When the investigators combined irinotecan and interferon, more than 80 percent of colon cancer cells with IRF5 proteins died. Only 28 percent of cells died in lines with IRF5 proteins knocked out and treated with both drugs. Irinotecan alone killed 65 percent of colon cancer cells that contained IRF5 proteins.
http://www.hopkinsmedicine.org/Press_releases/2005/08_15_05.html
Cancer Res 15 Aug. 2005; 65(16):7403-7412.
http://cancerres.aacrjournals.org
(Cancer Research is available online only from a Welch Library terminal. For more information see http://www.welch.jhu.edu/eresources/notice_aacr.html .)
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NEWS BRIEFS:
Leroy Hood To Give Sept. 29 Lecture -- The Fifth Annual William Wallace Scott Research Lectureship will be given by Leroy Hood, President of the Institute for Systems Biology in Seattle, WA, beginning at 8 a.m., Thursday, September 29, in Hurd Hall. The title of his lecture is "Systems Biology and Predictive Medicine." The lectureship is sponsored by The James Buchanan Brady Urological Institute.
100+ Women Professors Gala Nov. 1 -- The Johns Hopkins University School of Medicine in Baltimore, Maryland is celebrating the promotion of more than 100 women to the rank of Full Professor since its founding in 1893. All are invited to the celebration, which will include a day of scientific lectures by internationally acclaimed women scientists including a keynote address by the co-recipient of the 2004 Nobel Prize in Medicine, Linda Buck. To review the program and to register for the event, visit:
http://100womengala.onc.jhmi.edu/
Solomon Snyder on the value of the scientific literature in New Scientist. "Most scientific papers are probably wrong," by Kurt Kleiner, New Scientist, Aug. 30, 2005.
http://www.newscientist.com/article.ns?id=dn7915&feedId=online-news_rss20
http://www.jhu.edu/clips/2005_08/30/wrong.html
(Must be at a Hopkins computer to access this page.)
Doug Kerr on stem cells' potential in transverse myelitis on the CBS Early Show. "Stem Cells May Be Her Only Hope," the CBS Early Show, Aug. 1, 2005.
http://www.cbsnews.com/stories/2005/08/01/earlyshow/health/main713122.shtml
http://www.jhu.edu/clips/2005_08/30/stemcell.html
(Must be at a Hopkins computer to access this page.)
Hal Dietz on the "anti-aging" gene klotho on NationalGeographic.com. "Protein may limit brain and nerve cell death," by Brian Handwerk, NationalGeographic.com, Aug. 26, 2005.
http://news.nationalgeographic.com/news/2005/08/0825_050825_aging.html
http://www.jhu.edu/clips/2005_08/26/anti.html
(Must be at a Hopkins computer to access this page.)
Hal Dietz on the "anti-aging" gene klotho in Science. "Boosting gene extends mouse life-span," by Jennifer Couzin, Science, Aug. 26, 2005.
http://www.sciencemag.org/cgi/content/full/309/5739/1310a
http://www.jhu.edu/clips/2005_08/26/phys.html
(Must be at a Hopkins computer to access this page.)
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John Sales contributed to the Research Highlights for this issue.
Find "Change" and "Basics" online from a Hopkins computer:
http://www.insidehopkinsmedicine.org/change
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http://www.hopkinsmedicine.org/webnotes/
For more news from Hopkins, see:
http://www.hopkinsmedicine.org/Press_releases/index.html
Upcoming lectures and seminars:
http://www.hopkinsmedicine.org/faculty_staff/scicalendar.html
Find other news stories about Hopkins at:
http://www.insidehopkinsmedicine.org and click on "News Clips"
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--JHMI--
